An intrinsic brain system composed of phylogenetically ancient subcortical midline structures has been postulated as a mediator in the modulation and inhibition of sensitivity of painful stimuli. The goal of the research outlined in this proposal is a behavioral analysis of the significance of this system and of the endogenous mechanisms which regulate pain perception in animals. The studies will be carried out in rats and constitute a detailed analysis of stress-produced analgesia as a prototypical example of the functioning under physiological conditions of the postulated endogenous pain regulatory system. The following studies will be carried out: a) the relationship of stress-produced analgesia to morphine-produced and stimulation-produced analgesia will be investigated by examining the development or lack thereof of cross-tolerance between these various types of analgesia; b) the relationship between stress-produced analgesia and endorphin levels will be examined; c) the role of the pituitary in the mediation of stress-produced analgesia will be investigated; d) and lastly, the role of neurotransmitter systems in the mediation of stress-produced analgesia will be studied.